{"id":{"repo_id":"whiterose","oai_identifier":"oai:etheses.whiterose.ac.uk:570"},"canonical_url":"https://search.dev.ndltd.org/etd/whiterose/oai:etheses.whiterose.ac.uk:570","repository":{"repo_id":"whiterose","name":"White Rose University Consortium","base_url":"https://etheses.whiterose.ac.uk/cgi/oai2"},"display":{"title":"Structural and functional studies of intrinsically disordered fibronectin-binding proteins","abstract":"Bacterial fibronectin-binding proteins (FnBPs) mediate adhesion of bacteria to host tissues through binding to the human protein fibronectin (Fn). FnBPs are predicted to contain a series of intrinsically disordered Fn-binding repeats (FnBRs), which undergo a disorder-to-order transition on binding up to five F1-modules (1−5F1) from the N terminal domain of Fn through a tandem β-zipper interaction. This work investigated these predictions for SfbI-5, an FnBR from the important human pathogen Streptococcus pyogenes. SfbI-5 was shown to behave as an intrinsically disordered protein (IDP), with no stable secondary or tertiary structure. The C terminal third of SfbI 5 was shown to have propensity for β-strand conformations and, thus, might contain a preformed contact site involved in the initial interaction between SfbI-5 and 1−5F1. A high resolution structure of an SfbI-5 peptide in complex with 2F13F1 demonstrated that peptide binding occurs through formation of a tandem β-zipper with the concomitant formation of a large, extended intermolecular interface. Conserved FnBR residues play roles similar to those played by residues in related complexes involving Staphylococcus aureus FnBRs. The effect of mutating these residues on SfbI-5 binding to 1−5F1 was shown to be modest, suggesting that large, extended interfaces, when formed by IDPs, might be tolerant to mutations in the IDP. A putative FnBR, TickFnBR, was identified in a salivary protein from the blood-feeding tick Ixodes scapularis, which is a vector for human diseases. TickFnBR was shown to bind to 1−5F1 and also to Fn in human plasma. A high resolution structure demonstrated that a TickFnBR peptide binds to 2F13F1 through a tandem β-zipper. TickFnBR is the first eukaryotic FnBR to be identified, suggesting the tandem β zipper interaction is a useful mechanism for harmful organisms to target and exploit human Fn.","abstract_html":"Bacterial fibronectin-binding proteins (FnBPs) mediate adhesion of bacteria to host tissues through binding to the human protein fibronectin (Fn). FnBPs are predicted to contain a series of intrinsically disordered Fn-binding repeats (FnBRs), which undergo a disorder-to-order transition on binding up to five F1-modules (1−5F1) from the N terminal domain of Fn through a tandem β-zipper interaction. This work investigated these predictions for SfbI-5, an FnBR from the important human pathogen Streptococcus pyogenes. SfbI-5 was shown to behave as an intrinsically disordered protein (IDP), with no stable secondary or tertiary structure. The C terminal third of SfbI 5 was shown to have propensity for β-strand conformations and, thus, might contain a preformed contact site involved in the initial interaction between SfbI-5 and 1−5F1. A high resolution structure of an SfbI-5 peptide in complex with 2F13F1 demonstrated that peptide binding occurs through formation of a tandem β-zipper with the concomitant formation of a large, extended intermolecular interface. Conserved FnBR residues play roles similar to those played by residues in related complexes involving Staphylococcus aureus FnBRs. The effect of mutating these residues on SfbI-5 binding to 1−5F1 was shown to be modest, suggesting that large, extended interfaces, when formed by IDPs, might be tolerant to mutations in the IDP. A putative FnBR, TickFnBR, was identified in a salivary protein from the blood-feeding tick Ixodes scapularis, which is a vector for human diseases. TickFnBR was shown to bind to 1−5F1 and also to Fn in human plasma. A high resolution structure demonstrated that a TickFnBR peptide binds to 2F13F1 through a tandem β-zipper. TickFnBR is the first eukaryotic FnBR to be identified, suggesting the tandem β zipper interaction is a useful mechanism for harmful organisms to target and exploit human Fn.","abstract_has_math":false,"creators":["Norris, Nicole Catherine"],"institution":"University of York","degree_name":"Ph.D","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Potts, Jennifer R"],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-12","date_published":"2009-12","updated_at":"2026-07-24T06:03:17Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["uk.bl.ethos.547366"],"render_values":[{"text":"uk.bl.ethos.547366","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Potts, Jennifer R"]},{"key":"dc:creator","label":"Author","values":["Norris, Nicole Catherine"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2009-12-11"]},{"key":"dc:date.issued","label":"Date","values":["2009-12"]},{"key":"dc:publisher.commercial","label":"Dc Publisher Commercial","values":["University of York"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Biology (York)"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of York"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://etheses.whiterose.ac.uk/id/eprint/570/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["uk.bl.ethos.547366"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://etheses.whiterose.ac.uk/id/eprint/570/1/NCNorris_Thesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Bacterial fibronectin-binding proteins (FnBPs) mediate adhesion of bacteria to host tissues through binding to the human protein fibronectin (Fn). FnBPs are predicted to contain a series of intrinsically disordered Fn-binding repeats (FnBRs), which undergo a disorder-to-order transition on binding up to five F1-modules (1−5F1) from the N terminal domain of Fn through a tandem β-zipper interaction. This work investigated these predictions for SfbI-5, an FnBR from the important human pathogen Streptococcus pyogenes. SfbI-5 was shown to behave as an intrinsically disordered protein (IDP), with no stable secondary or tertiary structure. The C terminal third of SfbI 5 was shown to have propensity for β-strand conformations and, thus, might contain a preformed contact site involved in the initial interaction between SfbI-5 and 1−5F1. A high resolution structure of an SfbI-5 peptide in complex with 2F13F1 demonstrated that peptide binding occurs through formation of a tandem β-zipper with the concomitant formation of a large, extended intermolecular interface. Conserved FnBR residues play roles similar to those played by residues in related complexes involving Staphylococcus aureus FnBRs. The effect of mutating these residues on SfbI-5 binding to 1−5F1 was shown to be modest, suggesting that large, extended interfaces, when formed by IDPs, might be tolerant to mutations in the IDP. A putative FnBR, TickFnBR, was identified in a salivary protein from the blood-feeding tick Ixodes scapularis, which is a vector for human diseases. TickFnBR was shown to bind to 1−5F1 and also to Fn in human plasma. A high resolution structure demonstrated that a TickFnBR peptide binds to 2F13F1 through a tandem β-zipper. TickFnBR is the first eukaryotic FnBR to be identified, suggesting the tandem β zipper interaction is a useful mechanism for harmful organisms to target and exploit human Fn."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Structural and functional studies of intrinsically disordered fibronectin-binding proteins"]}]}],"canonical_facts":{"dc:contributor.advisor":["Potts, Jennifer R"],"dc:creator":["Norris, Nicole Catherine"],"dc:date":["2009-12-11"],"dc:date.issued":["2009-12"],"dc:description.abstract":["Bacterial fibronectin-binding proteins (FnBPs) mediate adhesion of bacteria to host tissues through binding to the human protein fibronectin (Fn). FnBPs are predicted to contain a series of intrinsically disordered Fn-binding repeats (FnBRs), which undergo a disorder-to-order transition on binding up to five F1-modules (1−5F1) from the N terminal domain of Fn through a tandem β-zipper interaction. This work investigated these predictions for SfbI-5, an FnBR from the important human pathogen Streptococcus pyogenes. SfbI-5 was shown to behave as an intrinsically disordered protein (IDP), with no stable secondary or tertiary structure. The C terminal third of SfbI 5 was shown to have propensity for β-strand conformations and, thus, might contain a preformed contact site involved in the initial interaction between SfbI-5 and 1−5F1. A high resolution structure of an SfbI-5 peptide in complex with 2F13F1 demonstrated that peptide binding occurs through formation of a tandem β-zipper with the concomitant formation of a large, extended intermolecular interface. Conserved FnBR residues play roles similar to those played by residues in related complexes involving Staphylococcus aureus FnBRs. The effect of mutating these residues on SfbI-5 binding to 1−5F1 was shown to be modest, suggesting that large, extended interfaces, when formed by IDPs, might be tolerant to mutations in the IDP. A putative FnBR, TickFnBR, was identified in a salivary protein from the blood-feeding tick Ixodes scapularis, which is a vector for human diseases. TickFnBR was shown to bind to 1−5F1 and also to Fn in human plasma. A high resolution structure demonstrated that a TickFnBR peptide binds to 2F13F1 through a tandem β-zipper. TickFnBR is the first eukaryotic FnBR to be identified, suggesting the tandem β zipper interaction is a useful mechanism for harmful organisms to target and exploit human Fn."],"dc:format":["text"],"dc:identifier":["uk.bl.ethos.547366"],"dc:identifier.uri":["https://etheses.whiterose.ac.uk/id/eprint/570/1/NCNorris_Thesis.pdf"],"dc:publisher.commercial":["University of York"],"dc:publisher.department":["Biology (York)"],"dc:publisher.institution":["University of York"],"dc:relation.isreferencedby":["https://etheses.whiterose.ac.uk/id/eprint/570/"],"dc:title":["Structural and functional studies of intrinsically disordered fibronectin-binding proteins"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D"]},"updated_at":"2026-07-24T06:03:17Z"}